Resistance Family

P-gp mediates the transport of a broad range of amphipathic hydro-phobic substrates which includes a variety of pharmacologically distinct agents used in cancer chemotherapy, hypertension, allergy, infection, immunosuppression, neurology, and inflammation (see review by Marzolini et al. (112)). 

Given the broad substrate specificity and the broad localization in various organs, it seems likely that genetic variability of this transporter may influence drug disposition as well as treatment efficacy. Accordingly, many studies related to the discovery of MDR1 polymorphisms and their effects on drug disposition or disease outcome have now been reported. 

BSEP also known as sister-P-glycoprotein (SPGP) was originally cloned from pig liver (185). BSEP is localized on the canalicular membrane of hepa-tocytes and is responsible for the secretion of bile salts across the canalicular membrane into bile. BSEP appears to be the predominant bile salt efflux system for hepatocytes, and is a critical component in the enterohepatic circulation of bile acids. A number of mutations in the transporter were found to the basis for progressive familial intrahepatic cholestasis type 2 (PFIC2) (186-188). Mutations found in PFIC2 patients include frameshifts, missense mutations, and premature termination codons. Most PFIC2 patients lack immunohistochemically detectable BSEP in their liver. Recently, seven 

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An alternative to most of these mechanisms is the existence of efficient efflux systems, so that toxic concentrations of the drug are not achieved. There are three major families of proton-dependent multidrug efflux systems (1) the major facilitator superfamily, (2) the small multidrug resistance family, and (3) the resistance/nodulation/cell division family (Paulsen et al. 1996). It should be emphasized that several of these systems are involved not with antibiotic efflux but with, for example, acriflavine, chlorhexidine, and crystal violet. An attempt is made only to outline a few salient features of the resistance/nodulation/cell division family that mediates antibiotic efflux, and these are given in Table 3.3 (Nikaido 1996). They consist of a transporter, a linker, and an outer membrane channel. 

An extensive new Section 10 is devoted to polymers, rubbers, fats, oils, and waxes. A discussion of polymers and rubbers is followed by the formulas and key properties of plastic materials. Eor each member and type of the plastic families there is a tabulation of their physical, electrical, mechanical, and thermal properties and characteristics. A similar treatment is accorded the various types of rubber materials. Chemical resistance and gas permeability constants are also given for rubbers and plastics. The section concludes with various constants of fats, oils, and waxes. 

DNQ—novolac resist chemistry has proved to have remarkable dexibiUty and extendibiUty. First introduced for printing appHcations, DNQ—novolac resists have been available since the eady 1960s in formulations intended for electronics appHcations. At present, most semiconductor manufacturing processes employ this resist chemistry. Careful contemporary research and engineering support the continuing refinement of this family of materials. 

Interferons (lENs) (52,53), a family of species-specific vertebrate proteins, confer nonspecific resistance to a broad range of viral infections, affect cell proliferation, and modulate immune responses. AH three principal interferons, a-interferon (lEN-a) produced by blood leucocytes, P-interferon (lEN-P) by fibroblasts, and y-interferon (lEN-y) by lymphocytes, also have antiviral activity. The abiUty of interferons to inhibit growth of transplantable and carcinogen-induced tumor led to research showing the direct antiproliferative and indirect immune-mediated antitumor activities (see Chemotherapeutics, anticancer). IENs have been found to be efficacious in certain malignancies and viral infections, eg, hairy cell leukemia (85% response) and basal cell carcinoma (86% response). However, the interferons do have adverse side effects (54). 

Insulin and Amylin. Insulin is a member of a family of related peptides, the insulin-like growth factors (IGFs), including IGF-I and IGF-II (60) and amylin (75), a 37-amino acid peptide that mimics the secretory pattern of insulin. Amylin is deficient ia type 1 diabetes meUitus but is elevated ia hyperinsulinemic states such as insulin resistance, mild glucose iatolerance, and hypertension (33). Insulin is synthesized ia pancreatic P cells from proinsulin, giving rise to the two peptide chains, 4. and B, of the insulin molecule. IGF-I and IGF-II have stmctures that are homologous to that of proinsulin (see INSULIN AND OTHER ANTIDIABETIC DRUGS). 

Demands for improved efficiency in aircraft gas turbines led to the use of a family of age hardenable, controlled expansion superaHoys for engine seals and casings. INCOLOY aHoys 903 [61107-16-2] (UNS N19903), 907 [107652-23-3] (UNS N19907), and 909 evolved from a continuing effort to improve the environmental resistance of this Cr-free, Fe—Ni—Co based system. 

Llthol Reds. Lithol Red or Pigment Red 49 1/7103-38-4] is one of the most important of the precipitated salt pigments. They comprise a family of sodium (PR 49), barium (PR 49 1), calcium (PR 49 2), and strontium (PR 49 3) salts of dia2oti2ed Tobias acid or 2-naphthylamine-l-sulfonic acid coupled with 2-naphthol. The most popular are the barium and calcium salts, the former being yellower in shade. These reds are used where brightness, bleed resistance, and low cost ate of primary importance. They are neither resistant to heat nor chemicals, and are used primarily in printing inks and some inexpensive air-dried industrial paints where good durabiUty is not requited. 

Nylon. Nylons comprise a large family of polyamides with a variety of chemical compositions (234,286,287). They have excellent mechanical properties, as well as abrasion and chemical resistance. However, because of the need for improved performance, many commercial nylon resins are modified by additives so as to improve toughness, heat fabrication, stabiUty, flame retardancy, and other properties. 

Polysulfones also offer desirable properties for cookware appHcations, eg, microwave transparency and environmental resistance to most common detergents. Resistance to various sterilizing media (eg, steam, disinfectants, and gamma radiation) makes polysulfones the resin family of choice for many medical devices. Uses in the electrical and electronic industry include printed circuit boards, circuit breaker components, connectors, sockets, and business machine parts, to mention a few. The good clarity of PSF makes it attractive for food service and food processing uses. Examples of appHcations in this area include coffee decanters and automated dairy processing components. 

ARALL laminates, a family of hybrid composites consisting of aramid fibers bonded with epoxy between 0.3 mm thick aircraft ahoy sheets, were introduced in the 1980s (53). The laminates have lower density than even the new Al—Li ahoys and are greatly superior to monolithic aluminum sheet in resisting the growth of fatigue cracks. ARALL laminates have been specified for aircraft stmcture which is subjected to cycHc tension loads (see Laminates). 

Although the antibacterial spectmm is similar for many of the sulfas, chemical modifications of the parent molecule have produced compounds with a variety of absorption, metaboHsm, tissue distribution, and excretion characteristics. Administration is typically oral or by injection. When absorbed, they tend to distribute widely in the body, be metabolized by the Hver, and excreted in the urine. Toxic reactions or untoward side effects have been characterized as blood dyscrasias crystal deposition in the kidneys, especially with insufficient urinary output and allergic sensitization. Selection of organisms resistant to the sulfonamides has been observed, but has not been correlated with cross-resistance to other antibiotic families (see Antibacterial AGENTS, synthetic-sulfonamides). 

The Tribaloy aUoy T-800, is from an aUoy family developed by DuPont in the eady 1970s, in the search for resistance to abrasion and corrosion. Excessive amounts of molybdenum and sUicon were aUoyed to induce the formation during solidifica tion of hard and corrosion-resistant intermetaUic compounds, known as Laves phase. The Laves precipitates confer outstanding resistance to abrasion, but limit ductUity. As a result of this limited ductUity the aUoy is not generaUy used in the form of plasma-sprayed coatings. 

Specialty mbbers, to which ACM belongs, are selected on the basis of their performance. As a consequence, many elastomeric families may compete for the same appHcation. A first selection can be carried out on the basis of oil and temperature resistance, according to ASTM D2000 (Fig. 4). 

A new family of peroxide-cured dipolymers was introduced in 1991. The peroxide cure provides copolymers that cure faster and exhibit good compression set properties without a postcure. The removal of the cure-site has also made the polymer less susceptible to attack from amine-based additives. By varying the methyl acrylate level in the dipolymer, two offerings in this family have been synthesized, VAMAC D and its more oil-resistant... 

Copolymers of propylene and tetrafluoroethylene, which are sold under the Aflas trademark by 3M, have been added to the fluorocarbon elastomer family (21—26). Also 3M has introduced an incorporated cure copolymer of vinyUdene fluoride, tetrafluoroethylene and propylene under the trademark Fluorel 11 (27). These two polymers (Aflas and Fluorel 11) do not contain hexafluoropropylene. The substitution of hexafluoropropylene with propylene is the main reason why these polymers show excellent resistance toward high pH environments (28). Table 1 Hsts the principal commercial fluorocarbon elastomers in 1993. 

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